To determine whether an agent such as WY-41,747, a long-acting somatostatin analogue, could be useful as an adjunct to insulin in the treatment of diabetes mellitus, postprandial plasma glucose concentrations were determined in subjects with insulin-dependent diabetes rendered euglycemic with the Biostator insulin infusion device under four conditions: (1) subcutaneous minipump infusion of insulin alone (13 +/- 1 units) over 30 minutes beginning 30 minutes before ingestion of a meal using insulin doses determined by the Biostator; (2) the same conditions as 1 but beginning immediately before meal ingestion; (3) the same conditions as 1 but with less insulin (7 +/- 1 units) accompanied by the analogue (0.01-0.05 mg/kg); (4) the same conditions as 2 but with the analogue and less insulin (11 +/- 1 units). Administration of the somatostatin analogue increased the effectiveness of insulin in controlling postprandial hyperglycemia and permitted satisfactory postprandial glycemic control when the insulin infusion was initiated immediately before meal ingestion. Administration of the analogue suppressed postprandial plasma glucagon and triglyceride concentrations and delayed xylose absorption. These results suggest that subcutaneous administration of a long-acting somatostatin analogue such as WY-41,747 along with insulin may be clinically useful in the treatment of diabetes mellitus.